HIV Infection Is Associated with Increased Fatty Infiltration of the Thigh Muscle with Aging Independent of Fat Distribution.

BACKGROUND: Lower muscle density on computed tomography (CT) provides a measure of fatty infiltration of muscle, an aspect of muscle quality that has been associated with metabolic abnormalities, weakness, decreased mobility, and increased fracture risk in older adults. We assessed the cross-sectional relationship between HIV serostatus, age, thigh muscle attenuation, and thigh muscle cross-sectional area (CSA). METHODS: Mean CT-quantified Hounsfield units (HU) of the thigh muscle bundle and CSA were evaluated in 368 HIV-infected and 145 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) Cardiovascular Substudy using multivariable linear regression. Models all were adjusted for HIV serostatus, age, race, and body mass index (BMI); each model was further adjusted for covariates that differed by HIV serostatus, including insulin resistance, hepatitis C, malignancy, smoking, alcohol use, and self-reported limitation in physical activity. RESULTS: HIV-infected men had greater thigh muscle CSA (p<0.001) but lower muscle density (p<0.001) compared to HIV-uninfected men. Muscle density remained lower in HIV-infected men (p = 0.001) when abdominal visceral adiposity, and thigh subcutaneous adipose tissue area were substituted for BMI in a multivariable model. Muscle density decreased by 0.16 HU per year (p<0.001) of increasing age among the HIV-infected men, but not in the HIV-uninfected men (HIV x age interaction -0.20 HU; p = 0.002). CONCLUSION: HIV-infected men had lower thigh muscle density compared to HIV-uninfected men, and a more pronounced decline with increasing age, indicative of greater fatty infiltration. These findings suggest that lower muscle quality among HIV-infected persons may be a risk factor for impairments in physical function with aging.

A mysterious gram-positive rods.

We encountered a patient with a history of intravenous drug use presenting with fever, malaise and nausea who was found to have cavitary lung lesions. Unexpectedly, gram positive rods grew out on day five on multiple blood cultures, which were later identified as Mycobacterium fortuitum. The patient underwent transesophageal echocardiogram, which showed aortic and tricuspid valve vegetations. Liver biopsy demonstrated granulomatous hepatitis. Interestingly, serum alkaline phosphatase level fell with antibiotic treatment. Mycobacterium fortuitum is ubiquitous worldwide, being found in tap water, and soil. M. fortuitum is usually considered as a contaminant. Disseminated infection caused by this bacterium in an immunocompetent host is extremely rare. Most of the disseminated infections have been reported in immune-deficient patients. In immunocompetent people, M. fortuitum causes human infection primarily by direct inoculation, including localized post-traumatic and surgical wound infections, and catheter-related sepsis. Our patient, an HIV-negative intravenous drug user, had Mycobacterium fortuitum sepsis associated with infective endocarditis, septic pulmonary emboli, and granulomatous hepatitis. Interestingly, the patient admitted using tap water occasionally for mixing heroin when her sterile water ran out, which we thought was the likely source of M. fortuitum.

Pulmonary adenocarcinomas with ground-glass attenuation on thin-section CT: quantification by three-dimensional image analyzing method.

PURPOSE: The purpose of this study was to evaluate software designed to calculate whole tumor volumes and the ratio of the solid component to whole volume (%solid) in pulmonary nodules with ground-glass opacity in three dimensions. METHODS: The study included 49 patients with histologically diagnosed adenocarcinomas smaller than 2 cm in diameter. The %solid was calculated both automatically using new software, and by manual measurement of the following four parameters by two observers: the ratio of the largest diameter (a) and the area (b) at the mediastinal window to those at the lung window, and the ratio of the largest diameter (c) and the area (d) of the solid component to those of the ground-glass component at the lung window. Agreement of intra- and inter-observer data by both Spearman's rank correlation test and Bland-Altman's method, and a comparison by Spearman's rank correlation test of the %solid in both Noguchi sub-classifications and vessel invasion in histologic specimens, between the software and manual methods, were assessed. RESULTS: Of the 49 nodules, 48 were successfully measured and assessed. The agreement of the observers with the software was better (Bland-Altman's method; mean difference, -0.3%; 95% limits of agreement, -3.1 to 2.5%) than with the manual measurements (a: 5.3%, -17.6 to 28.3%; b: 8.3%, -10.6 to 26.9%; c: 10.7%, -17.6 to 39%; d: 6.4%, -22 to 34.8%). The correlation between %solid and the histological group was worse with the software (Spearman's rank correlation test; r=0.487, p<0.001) than with the manual method (a, r=0.534; b, r=0.557; c, r=0.552; d, r=0.545). CONCLUSION: Although the software requires improvement in the calculation of %solid with volumetric analysis, this is a reproducible and promising quantitative method for determining the grades of malignancy of small lung cancers.

Volume histogram analysis for lung thin-section computed tomography: differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia.

OBJECTIVE: The aim of this study was to evaluate volume histogram analysis between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). METHODS: Sixty cases (UIP, n = 22; NSIP, n = 38) were evaluated retrospectively. Three parameters (contrast, variance, and entropy) were calculated in 3 types of regions of interest (ROIs): (a) whole lung, (b) right lower lobe, and (c) cubic ROIs. To evaluate the influence of extent of abnormal findings, the numbers of voxels with low or high density in whole lung were compared with the 3 parameters. RESULT: No significant differences were observed between the ROIs of whole lung and the right lower lobe. In all cubic ROIs, entropy in UIP was larger than that in NSIP (P < 0.001). The numbers of voxels with low-density areas significantly correlated with the values of contrast and entropy, whereas those with high-density areas significantly correlated with all 3 parameters. CONCLUSION: Volume histogram analysis for cubic ROIs may be feasible for differentiating between UIP and NSIP.

Pulmonary cavitary nodules on computed tomography: differentiation of malignancy and benignancy.

OBJECTIVE: To establish computed tomographic findings that enable accurate differentiation between malignant and benign cavitary lung nodules. METHODS: Computed tomographic scans from 39 patients with malignant cavitary nodules and from 39 patients with benign cavitary nodules were independently assessed by 2 observers. They recorded the computed tomographic findings of both types of cavitary nodules and surrounding pulmonary parenchyma. The computed tomographic findings were then compared using chi test. RESULTS: The notch was found in 29% of benign cavitary nodule cases and in 54% of malignant cavitary nodule cases (P < 0.01). An irregular internal wall was found in 26% of benign nodules and in 49% of malignant nodule cases (P < 0.01). A linear margin (P < 0.01), satellite nodule presence (P < 0.01), bronchial wall thickening (P < 0.05), consolidation (P < 0.05), and ground-glass attenuation (P < 0.01) were significantly more frequent in benign cavitary nodules than in malignant ones. CONCLUSIONS: Although the computed tomographic findings of benign and malignant cavitary nodules overlap, some computed tomographic findings are useful for differentiating cavitary nodules.

Pulmonary nodules: 3D volumetric measurement with multidetector CT--effect of intravenous contrast medium.

PURPOSE: To retrospectively evaluate the effect of contrast medium on the three-dimensional volumetric measurement of pulmonary nodules. MATERIALS AND METHODS: The study was approved by the local institutional review committee, with waiver of informed consent. Sixty pulmonary nodules in 60 patients (17 women, 43 men; age range, 29-82 years) were imaged before and after administration of contrast medium with a 64-channel multidetector computed tomographic (CT) scanner; reconstructed images with a section thickness of 0.625 mm were obtained by using a bone algorithm and a standard algorithm. Volumetric measurements of pulmonary nodules were performed by using commercially available software, and the postcontrast volume ratio was calculated by dividing the postcontrast volume by the precontrast volume. Precontrast and postcontrast volumes were then analyzed by using a Wilcoxon signed rank test. RESULTS: The median measured volumes of pulmonary nodules were 817 mm(3) (precontrast imaging, bone algorithm), 887 mm(3) (postcontrast imaging, bone algorithm), 812 mm(3) (precontrast imaging, standard algorithm), and 855 mm(3) (postcontrast imaging, standard algorithm). The measured volumes obtained with the bone algorithm were significantly larger than those obtained with the standard algorithm, both before and after administration of contrast medium (P < .01); with both the standard algorithm and the bone algorithm, the measured postcontrast volumes were significantly larger than the precontrast volumes (P < .01). The postcontrast volume ratio was more than 1.0 in 45 cases (75%) when the bone algorithm was used and in 53 cases (88%) when the standard algorithm was used. The mean postcontrast volume ratio was 1.054 with the bone algorithm and 1.065 with the standard algorithm. CONCLUSION: The measured volume of pulmonary nodules obtained by using three-dimensional volumetric software increased after administration of contrast medium. Moreover, the measured volume of pulmonary nodules that was obtained with the bone algorithm was larger than that obtained with the standard algorithm, regardless of whether contrast medium was used.

Preoperative assessment of thymic veins on multidetector row CT: optimization of contrast material volume.

PURPOSE: Preoperative localization of the thymic veins is considered important to prevent intraoperative severe bleeding prior to video-assisted thoracoscopic thymectomy. The purpose of this study was to determine the optimal dose of contrast material for preoperative CT imaging for the detection of thymic veins on the basis of patient weight. MATERIALS AND METHODS: The records of 31 patients who underwent thymectomy were examined retrospectively. All patients were scanned using an eight-channel multidetector-row computed tomography (CT) scanner at 1.25 mm collimation and a 0.625-mm reconstruction interval. CT scans were obtained after injection of 300 mg I/ml nonionic contrast material at a rate of 2 ml/s. A 90-ml contrast bolus was used for the first 16 consecutive patients (group I), and a 150-ml bolus was used for the following 15 patients (group II). The scan delay was 60 s and 90 s in groups I and II respectively. Two independent radiologists who were blinded to the surgical results evaluated the number of thymic veins observed on preoperative CT, which was later correlated with the actual number of thymic veins clipped during surgery. The responses were analyzed with respect to contrast amount by single bolus and per kilogram of body weight. RESULTS: Thymic veins were correctly detected in 9 of 16 (56%) patients in group I and 14 of 15 (93%) patients in group II. Thymic vein detection was significantly better in patients who received the >or=2.0 ml/kg contrast medium compared to those who received the 1.00-1.99 ml/kg medium (P < 0.05). CONCLUSION: An intravenous contrast material volume of 2 ml/kg (300 mg I/ml) is appropriate for the identification of thymic veins on prethymectomy CT.

Interferon alpha receptors are important for antiproliferative effect of interferon-alpha against human hepatocellular carcinoma cells.

AIM: Interferon (IFN)-alpha is a promising drug for the prevention and treatment of hepatocellular carcinoma (HCC). We reported that responders to IFN-alpha/5-fluorouracil combination therapy expressed higher IFN alpha receptor (IFNAR)2 in tumor. Herein we studied involvement of IFNARs in response to IFN-alpha in HCC cells. METHODS: IFN-alpha sensitivity and expression of IFNARs were studied in six HCC cell lines (HuH7, PLC/PRF/5, HLE, HLF, HepG2, Hep3B) using growth-inhibitory and RT-PCR, Western blot assays. Short interfering RNAs (SiRNAs) against IFNAR1 and 2 were used to analyze the role of the IFNARs in IFN-alpha's effect and signal transduction. RESULTS: The expressions of IFNAR1 and 2c mRNAs were higher in PLC/PRF/5 cells than those in other cell lines, and PLC/PRF/5 cells expressed abundant IFNAR2c on their cell membrane. When we examined the sensitivity of the HCC cell lines to the growth-inhibitory effect of IFN-alpha, PLC/PRF/5 exhibited a significant response, while the other cells were much more resistant. Knockdown of either IFNAR1 or 2 using siRNAs suppressed the IFN-alpha's signal transduction (2.5-fold), and decreased the growth-inhibitory effect (down by 69.9% and 67.3%). CONCLUSION: The results suggest that the expression of IFNAR1 and IFNAR2c independently are important for the antiproliferative effect of IFN-alpha in HCC cells.

Computer-assisted lung nodule volumetry from multi-detector row CT: influence of image reconstruction parameters.

PURPOSE: To investigate differences in volumetric measurement of pulmonary nodules caused by changing the reconstruction parameters for multi-detector row CT. MATERIALS AND METHODS: Thirty-nine pulmonary nodules less than 2 cm in diameter were examined by multi-slice CT. All nodules were solid, and located in the peripheral part of the lungs. The resultant 48 parameters images were reconstructed by changing slice thickness (1.25, 2.5, 3.75, or 5 mm), field of view (FOV: 10, 20, or 30 cm), algorithm (high-spatial frequency algorithm or low-spatial frequency algorithm) and reconstruction interval (reconstruction with 50% overlapping of the reconstructed slices or non-overlapping reconstruction). Volumetric measurements were calculated using commercially available software. The differences between nodule volumes were analyzed by the Kruskal-Wallis test and the Wilcoxon Signed-Ranks test. RESULTS: The diameter of the nodules was 8.7+/-2.7 mm on average, ranging from 4.3 to 16.4mm. Pulmonary nodule volume did not change significantly with changes in slice thickness or FOV (p>0.05), but was significantly larger with the high-spatial frequency algorithm than the low-spatial frequency algorithm (p<0.05), except for one reconstruction parameter. The volumes determined by non-overlapping reconstruction were significantly larger than those of overlapping reconstruction (p<0.05), except for a 1.25 mm thickness with 10 cm FOV with the high-spatial frequency algorithm, and 5mm thickness. The maximum difference in measured volume was 16% on average between the 1.25 mm slice thickness/10 cm FOV/high-spatial frequency algorithm parameters and overlapping reconstruction. CONCLUSION: Volumetric measurements of pulmonary nodules differ with changes in the reconstruction parameters, with a tendency toward larger volumes in high-spatial frequency algorithm and non-overlapping reconstruction compared to the low-spatial frequency algorithm and overlapping reconstruction.

Stronger growth-inhibitory effect of interferon (IFN)-beta compared to IFN-alpha is mediated by IFN signaling pathway in hepatocellular carcinoma cells.

Interferon (IFN) is a promising drug for prevention and treatment of hepatocellular carcinoma (HCC) in combination with chemotherapeutic agents. We previously reported that the spectra of antiproliferative activity and synergistic effect of IFN-beta when combined with anticancer drugs are more potent than those of IFN-alpha in HCC cells. However, the mechanism of the diverse antitumor effects of the IFNs is not understood yet. We studied the expression of IFN alpha receptor 2 (IFNAR2), STATs, and IFN-alpha, IFN-beta's growth-inhibitory effect, signal transduction and binding to IFNAR2 on three HCC cell lines and a tumor xenografted mouse model (12 animals/group). From the results, IFN-beta showed a significantly stronger growth-inhibitory effect than IFN-alpha on the HuH7 cell line (expressing low IFNAR2), however it was similarly high on PLC/PRF/5 and weak on HLE. In the nude mouse tumor xenograft model, IFN-beta injection significantly suppressed tumor volume relative to vehicle injection, while IFN-alpha showed weaker growth-inhibition. IFN signal transduction (phosphorylated-STAT1, 3) induced by IFN-beta was higher than that by IFN-alpha in HuH7 and tumor xenografts. Pretreatment of hepatoma cells with anti-IFNAR2 antibody blocked the IFN signaling, more for IFN-alpha. IFN-alpha's antiproliferative effect was reduced by the antibody in lower concentrations compared to that of IFN-beta. Taken together, the HCC cells that express low IFNAR2 and are resistant to IFN-alpha were sensitive to the growth-inhibitory effect of IFN-beta, which might be mediated by stronger IFN signal transduction and distinct binding to IFNAR compared to IFN-alpha.

Usual interstitial pneumonia and chronic idiopathic interstitial pneumonia: analysis of CT appearance in 92 patients.

PURPOSE: To retrospectively analyze computed tomographic (CT) findings of chronic idiopathic interstitial pneumonia (IIP) and to determine which findings are most helpful for distinguishing IIP from usual interstitial pneumonia (UIP) with univariate and multivariate analyses. MATERIALS AND METHODS: Institutional review board approval and informed consent were not required for this retrospective review of patient records and images. Two observers working independently and without knowledge of the diagnosis evaluated the extent and distribution of various thin-section CT findings (ground-glass opacity, consolidation, reticulation, and honeycombing) in 92 patients (51 men, 41 women; mean age, 56 years; age range, 29-81 years) with a histologic diagnosis of UIP (n = 20), cellular nonspecific interstitial pneumonia (NSIP) (n = 16), fibrotic NSIP (n = 16), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) (n = 11), desquamative interstitial pneumonia (DIP) (n = 15), or lymphoid interstitial pneumonia (LIP) (n = 14). Observers used univariate and multivariate statistical analyses to compare their findings with the extent and distribution of UIP. RESULTS: Observers made the correct diagnosis in 145 (79%) of 184 readings. Multivariate logistic regression analysis showed that the independent findings that distinguished UIP from cellular NSIP were the extent of honeycombing and the most proximal bronchus with traction bronchiectasis (odds ratio, 5.16 and 0.37, respectively); the finding that distinguished UIP from fibrotic NSIP was the extent of honeycombing (odds ratio, 2.10). CT features that distinguished UIP from RB-ILD and DIP included extent of ground-glass opacity (odds ratio, 0.76), thickening of bronchovascular bundles (odds ratio, 1.58), the most proximal bronchus with traction bronchiectasis (odds ratio, 0.22), and the number of segments with traction bronchiectasis (odds ratio, 3.64). CONCLUSION: UIP has a characteristic appearance that usually facilitates distinction from other types of chronic IIPs at thin-section CT. The most useful finding when differentiating UIP from NSIP was the extent of honeycombing.

MR imaging of thymic epithelial tumors: correlation with World Health Organization classification.

PURPOSE: The aim of this study was to determine magnetic resonance imaging (MRI) features of various subtypes of thymic epithelial tumors based on the World Health Organization classification. MATERIALS AND METHODS: The study included 64 patients with histologically proven thymic epithelial tumors. Two observers evaluated the MRI findings in terms of tumor size, contour, lobulation, shape, homogeneity, the presence of intratumor high- and low-signal foci, enhancement degree and pattern, the presence of capsule and septum, and associated mediastinal lymphadenopathy and pleural effusion. RESULTS: Type A tumors were more likely to have a smooth contour, round shape, distinct capsule, and smaller size compared to any other type of thymic epithelial tumor. Thymic carcinomas demonstrated a higher prevalence of low-signal foci within the mass on T2-weighted images and mediastinal lymphadenopathy than any other types. The frequency of heterogeneous intensity on T2-weighted images increased from type A tumors to thymic carcinomas. CONCLUSION: The presence of a smooth contour, round shape, and capsule is highly suggestive of a type A tumor. Foci of low signal intensity in the mass on T2-weighted images and mediastinal lymphadenopathy are highly suggestive of thymic carcinomas.

Quantitative analysis for computed tomography findings of various diffuse lung diseases using volume histogram analysis.

OBJECTIVES: : The aim of this study was to achieve the quantitative analysis of the characteristic computed tomography (CT) findings and course of interstitial pneumonia using the volume histogram method. METHODS: : Contrast (CNT), variance (VAR), and entropy (EPY) values from whole-lung volume data were compared between normal lungs and 5 diseases that have characteristic CT findings. Thirteen cases with nonspecific interstitial pneumonia (NSIP) were evaluated before and after treatment. RESULTS: : In cases with thickening of the bronchovascular bundles and interlobular thickening, ground-glass attenuation, airspace consolidation, and honeycombing, the values of VAR and EPY were greater than those in the normal cases (P < 0.05). In the cases with NSIP, the CNT value after treatment was significantly greater and the values of VAR and EPY after treatment were significantly lower than those before treatment (P < 0.05). CONCLUSIONS: : Volume histogram analysis is a promising method for the evaluation of diffuse lung diseases and the effectiveness of treatment.

TGF-beta1-induced cell growth arrest and partial differentiation is related to the suppression of Id1 in human hepatoma cells.

Transforming growth factor beta 1 (TGF-beta1) is a proposed regulator of Ids (inhibitors of DNA binding/differentiation) gene expression in epithelial cells. We previously reported that Id proteins are variously expressed in human hepatocellular carcinomas (HCC). However, the mechanism of regulation of Ids in HCC remains obscure. Here, we examined the relationship between Id1 and TGF-beta1 in four HCC cell lines, and studied the changes in cell proliferation, cell cycle and differentiation. The four HCC cell lines expressed Id1, TGF-beta1 and their receptors at various levels. TGF-beta1 strongly inhibited the growth of HuH7 cells, while the growth inhibition was moderate in PLC/PRF/5, and was not observed in HLE and HLF cell lines. TGF-beta1-induced growth inhibition in HuH7 cells was associated with cell accumulation in the G1 phase and partial induction of differentiation (with reduction of AFP and AFP-L3). Induction by TGF-beta1 dose-dependently suppressed Id1 expression in HuH7 cells; 1 ng/ml TGF-beta1 inhibited Id1 by 84.0 and 78.6% that of the untreated control at transcriptional and protein levels, respectively. HLE and HLF cells, which did not exhibit a TGF-beta1 growth inhibitory effect, lacked TGF-beta receptors and Id1 expression was not altered. In PLC/PRF/5 cells, Id1 augmentation was not observed in response to TGF-beta1, indicating that TGF-beta1-induced growth inhibition was not related to Id1 in this cell line. Our results suggest that, in some HCC cells, the pathway of suppression of Id1 by TGF-beta1 may be important in TGF-beta1-induced growth inhibition and partial differentiation.

Pulmonary mucosa-associated lymphoid tissue type lymphoma with increased accumulation of fluorine 18-fluorodeoxyglucose on positron emission tomography.

Mucosa-associated lymphoid tissue (MALT) type lymphoma has generally been thought not to show increased fluorine 18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET), based on previous research. Only a limited numbers of articles have been published on this topic, however, involving a small number of cases. Although positive FDG PET results might be uncommon in this entity, a case of increased FDG accumulation in a case of MALT type lymphoma of the lung is presented.